A Cross-Sectional Study Comparing the Efficacy of Various Growth Charts in Evaluating the Incidences of Small for Gestational Age and Large for Gestational Age at Birth Among Liveborn Neonates Delivered at a Tertiary Teaching Hospital

Background and objective Growth charts are important in monitoring the growth of neonates. The growth of Indian fetuses is understood to be different from the Western population due to multiple factors. In this study, we aimed to analyze the utility of the application of various growth charts in evaluating the birth weights of liveborn neonates at a tertiary teaching hospital. Methodology A total of 729 liveborn neonates between 24 to 42 weeks of gestation delivered at the study institute during the study period were included. Birth weights were plotted on three growth charts - Fenton 2013, INTERGROWTH-21st (IG-21), and Kandraju et al. chart - and classified as small for gestational age (SGA), or appropriate for gestational age (AGA), or large for gestational age (LGA) according to the respective centiles and sex. The incidences of SGA and LGA were calculated with respect to various charts and compared. Statistical analysis was done using the McNemar Chi-square test for paired categorical variables. Cohen’s kappa (K) was used to analyze the concordance between the growth charts. A p-value <0.005 was considered statistically significant. Results Among 668 term neonates, the number of neonates classified as SGA was 313 (46.86%), 236 (35.33%), and 219 (32.78%) according to Fenton 2013, IG-21, and Kandraju et al. chart respectively. The difference in incidences of SGA between Fenton 2013 and IG-21 for term neonates was significant (p=0.0001). The difference between incidences of SGA among term neonates according to Fenton 2013 and Kandraju et al. and IG-21 vs. Kandraju et al. was significant (p=0.0001). Among 61 preterm neonates, the number of neonates classified as SGA was 15, 11, and five according to Fenton 2013, IG-21, and Kandraju et al. respectively. There was no statistically significant difference between the three charts. Among 729 neonates, the number of neonates classified as LGA was 10 (1.37%), 22 (3.02%), and 32 (4.39%) according to Fenton 2013, IG-21, and Kandraju, et al. respectively. The difference in incidences of LGA between Fenton 2013 and IG-21 was significant (p=0.0015). The difference in incidences of LGA between Fenton 2013 and Kandraju et al. was significant (p=0.0001). The difference in incidences of LGA between IG-21 and Kandraju et al. was also significant (p=0.0044). Conclusion Fenton 2013, IG-21, and Kandraju et al. growth charts vary significantly in detecting the incidence of SGA and LGA among term neonates. Among term neonates, IG-21 and Kandraju et al. growth charts are comparable in terms of the estimation of SGA. The Fenton 2013 growth chart showed a higher incidence of SGA among term neonates. The incidence of LGA was highest according to Kandraju et al. growth chart and least according to Fenton 2013. Among preterm neonates, the incidence of SGA as per birth weight was comparable across the three growth charts.


Introduction
Birth weight is the single most important predictor of growth potential. Growth of the fetus varies not only among individuals but also across populations due to differences in ethnicity, geography, socioeconomic status, and environmental, nutritional, and hereditary factors [1][2][3]. Most of the available growth charts are based on the Western population. There are different types of growth charts such as reference growth charts and standard growth charts. Growth reference charts describe how neonates actually grow and are used to establish whether or not their measurements are typical of the reference group. Growth standard charts are essentially the same as growth reference charts except that the underlying reference sample is selected on health grounds. They pertain to a healthy pattern of growth. The standard charts show how the neonates ought to grow rather than how they do grow [4]. INTERGROWTH-21st (IG-21) is a standard growth chart developed based on data obtained from fetuses and neonates (26-32 weeks of gestational age) across eight countries from different regions of the world [5]. Fenton 2013 [6] is a reference growth chart published in 2013 for preterm neonates from 22 weeks to 50 weeks of gestational age. Kandraju et al. chart [7] is a regional growth chart based on the South Indian population published in 2011 based on the data from a level III maternity and newborn hospital-based study involving 31,391 neonates on birth weight across 24 to 42 weeks of gestational age.
Indian neonates are among the smallest in the world, especially compared to the neonatal population from developed countries [8]. Hence, when Indian neonates are classified using the Western-based charts, there is a risk of overestimation of small for gestational age (SGA) neonates as many appropriate for age (AGA) neonates could get classified as SGA and underestimation of large for gestational age (LGA) neonates. An accurate diagnosis of SGA and LGA is essential as the implications of this classification on the health of infants during the perinatal period and in the future are significant. The SGA and LGA neonates are at risk of developing metabolic syndromes later in life due to various pathophysiological changes that occur in utero [9][10][11]. In this study, we aimed to plot the birth weight of neonates using the centiles provided by the above three growth charts and to compare the incidences of SGA and LGA among infants as per the data from these charts.

Materials And Methods
This was a cross-sectional study conducted at a tertiary care teaching hospital in Hyderabad, Telangana, South India. A total of 729 liveborn neonates between 24 to 42 weeks of gestation were included in the study. The study was conducted from January 2020 to June 2021, after obtaining Institutional Ethical Committee (IEC) clearance (Mediciti Ethics Committee: dt:10/10/2019/S.No:11).
The sample size required was calculated based on the prevalence of SGA and LGA neonates as documented in previous studies. The prevalence of SGA was 46.9% based on the data gathered from previous birth cohort studies [12] and the prevalence of LGA was 9.4% [13]. Based on this data, the sample size was calculated with the formula n={z^2* p*(1-p)}/d^2, where n is the sample size, z is the confidence interval (which was taken as 95%), p is the prevalence observed in the population, and d is the margin of error taken as %. The sample size was 383 based on prevalence for SGA neonates and 131 for LGA neonates. With a 10% margin of error, the sample size required was determined to be 421.
The inclusion criteria were as follows: all liveborn neonates between 24 and 42 weeks of gestation delivered at the study institute during the study period. The exclusion criteria were as follows: intrauterine deaths and stillbirths, neonates with gross congenital anomalies, multiple pregnancies (twins, triplets, etc.), outborn neonates, and all liveborn neonates born after 42 weeks of gestational age. All the neonates who fulfilled the inclusion and exclusion criteria were consecutively sampled. Owing to the coronavirus disease 2019 (COVID-19) pandemic, the number of hospital deliveries was low during the study period, and a total of 729 neonates were finally enrolled.
Informed written consent was obtained from the parents of all neonates included in the study. A preformatted proforma was used to collect the relevant maternal and neonatal data. Maternal details such as age at conception, last menstrual period (LMP), stature, and socioeconomic status based on the Kuppuswamy scale [14], comorbidities present during pregnancy such as hypertension, diabetes mellitus, hypothyroidism, ultrasonogram reports during pregnancy, and drug intake if any were documented. For neonates, date and time of birth, birth weight, head circumference, and length along with general examination were documented. Birth weight was recorded within 10 minutes of birth after stabilizing the neonate. The weight was measured on a digital weighing machine with a variability of ±10 grams. The neonate was weighed three times and an average of the three readings was taken as the final birth weight. The other measurements were taken within 24 hours of birth. The gestational age was calculated as per LMP or first-trimester ultrasound (dating scan) when LMP was not available/reliable. The birth weight of all the neonates was plotted on Fenton 2013, IG-21, and Kandraju et al. growth charts. They were classified as SGA, AGA, and LGA according to the respective centiles and compared. SGA was defined as a weight below the 10th percentile for gestational age and gender as per the population growth charts. AGA was defined as the weight between the 10th percentile and 90th percentile for gestational age and gender as per the population growth charts.
LGA was defined as weight above the 90th percentile for gestational age and gender as per the population growth charts [15]. The incidences of SGA and LGA were calculated accordingly with respect to various charts.

Statistical analysis
Data were entered into a Microsoft Excel sheet and analyzed using IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY). Descriptive statistics were expressed as mean and standard deviation (SD) for continuous variables and as proportions and percentages for categorical variables. Inferential statistical analysis was done using McNemar's Chi-square test for paired categorical variables. Cohen's kappa (K) [16] statistic was used to analyze the concordance between the growth charts. A p-value <0.005 was considered statistically significant.

Results
In this cross-sectional study, out of 745 neonates, 16 neonates were excluded (seven twins, six intrauterine deaths, and three congenital anomalies), and 729 neonates (388 males) were included. Of them, 61 were preterm neonates and 668 were term neonates. The demographic characteristics of mothers and their comorbidities are listed in Table 1.

Variables Values
Mothers  Based on weight centiles of IG-21 charts, 11 neonates were SGA among the neonates born to 51 mothers with diabetes complicating the pregnancy; 29 neonates were SGA among the neonates born to 56 mothers with hypertension. Eight neonates were SGA among the neonates born to 29 mothers with hypothyroidism.
Among the 729 neonates, the classification of neonates as SGA, AGA, and LGA according to the three charts is presented in Table 2.  Among preterm neonates (n=61), the classification into SGA, AGA, and LGA according to the various charts is shown in Table 3.  The classification of term neonates into SGA, AGA, and LGA according to the various charts is presented in Table 4.  A comparison of the various charts with each other and their agreement by Cohen's K [17] is tabulated in Table 5.   Our findings are similar to those of a cross-sectional study done in 2019 by Tenório et al. [17] in Brazil. The authors observed that among 344 neonates between 33-43 weeks of gestational age (20 preterm  A study published by Tuzun et al. [22] in 2017 involving 248 preterm neonates showed the incidence of LGA as 6% according to both Fenton 2013 and IG-21. A study by Prakash et al. [23] from South India involving 2507 neonates observed discrepancies in the detection of LGA between Fenton 2013 (1.4%) and IG-21 (5.5%). These differences among the international charts that are generally used for labeling neonates as SGA and LGA are important and should not be overlooked. This study highlights the need for conducting large-scale population-specific studies on a national level that will help construct growth charts targeting our Indian neonates.

Limitations
This study was based on a small sample size with a relatively lower number of preterm neonates. Moreover, the study did not look into the causative factors (maternal, placental, or fetal) for SGA and LGA.

Conclusions
The Fenton 2013, IG-21, and Kandraju et al. growth charts vary significantly in detecting the incidence of SGA and LGA among term neonates. Among term neonates, IG-21 and Kandraju et al. growth charts are comparable for the estimation of SGA. The Fenton 2013 growth chart showed a higher incidence of SGA among term neonates. The incidence of LGA was highest according to Kandraju et al. growth chart and least according to the Fenton 2013 growth chart. Among preterm neonates, the incidence of SGA using birth weight was comparable across the three growth charts. It could be understood that while population-specific growth charts might be required for term neonates, all three charts are comparable and could be applied among preterm neonates.

Additional Information
Disclosures